The Research: The purpose of this research is to gain an understanding of how the normal alveolar macrophage regulates the persistent production of eicosanoids, potent inflammatory mediators (1-19). A persistent inflammatory response is present in a variety of pulmonary disorders such as sarcoidosis, asthma, etc. The alveolar macrophage is the most abundant inflammatory effector cell on the alveolar surface of the lung. In addition to its role as a phagocyte, the alveolar macrophage has the ability to regulate inflammation by producing a variety of both proinflammatory (LTB4, thromboxanes) and antiinflammatory eicosanoids (PGE2). In order to persistently produce these mediators, however, the alveolar macrophage must be able to persistently activate the first committed enzymes PGH synthase (for the generation of thromboxanes and prostaglandins) and 5-lipoxygenase (for the generation of leukotrienes). The candidate will evaluate the molecular mechanisms in human alveolar macrophages responsible for the persistent production of an active PGH synthase in Aims 1-4 and the mechanisms responsible for the activation of an inactive 5-lipoxygenase in Aim 5. In addition the candidate will evaluate the effects of monocyte to macrophage differentiation on eicosanoid release in Aim 6.